The purpose of this research proposal is both to advance the basic information we have about the control of collagen accumulation in scars which form after injury to tendon and nerve, and to explore the possible implications that this information may have for treatment of tendon injuries and nerve injuries in man. In previous work on this project, we developed animal models for tendon and nerve injries, and we have shown that systemic administration of a proline analogue, cis-hydroxyproline, improves the response to such injuries. Also, we have defined the unusual biochemical mechanism by which proline analogues inhibit the formation of collagen fibers. We here propose to develop several techniques whereby proline analogues can be administered locally and in a manner which allows their controlled release at the site of scar formation. A major part of the effort will be concentrated on the synthesis of absorbable polymers of cis-hydroxyproline and other proline analogues, and testing the effects of the polymers on the responses to tendon and nerve injury. We will also examine the effects of hydrogels impregnated with proline analogues and we will attempt to develop more effective proline analogues for local administration.